Antibodies represent a class of therapeutic molecules with applications in many different areas including transplantation, cardiovascular diseases, infectious diseases, cancer, and autoimmunity (Goldenberg, M., 1999, Clin. Ther. 21:309–318; Present, D. et al., 1999, New Engl. J. Med. 340:1398–1405; Targan, S. et al., 1997, New Engl. J. Med. 337:1029–1035; Davis, T. et al., 1999, Blood 94:88a; Saez-Llorens, X. et al., 1998, Pediatr. Infect. Dis. J. 17:787–791; Berard, J. et al., 1999, Pharmacotherapy 19:1127–1137; Glennie, M. et al. 2000, Immunol. Today 21:403–410; Miller, R., 1982, New Engl. J. Med. 306:517–522; Maini, R., et al., 1999, Lancet, 354:1932–1939). The development of hybridoma technology enabled the isolation of rodent monoclonal antibodies (also referred to as MAbs) as candidate therapeutic molecules (Kohler, G. and Milstein, C., 1975, Nature 256:495–497). However, early studies involving the use of non-human monoclonal antibodies for in vivo human therapy, demonstrated that human anti-mouse antibody (HAMA) responses could limit the use of such agents (Schroff, R. et al., 1985, Cancer Res. 45,879–885; Shawler, D. et al., 1985, J. Immunol. 135:1530–1535). Thus it is recognized that a reduction in the immunogenicity of therapeutic antibodies is desirable. Recombinant DNA technologies have been employed to reduce the immunogenicity of non-human antibodies (Boulianne, G. et al., 1984, Nature 312, 643–646; Morrison, S. et al., 1984, Proc. Natl. Acad. Sci. U.S.A. 81:6851–6855; Riechmann, L. et al., 1988, Nature 332:323–327; Jones, P. et al., 1986, Nature 321:522–525; Queen, C. et al., 1989, Proc. Natl. Acad. Sci. U.S.A. 86:10029–10033). However, it is also recognized that fully human monoclonal antibodies are a potential source of low immunogenicity therapeutic 30 agents for treating human diseases (Little, M. et al., 2000, Immunol. Today 21:364–70). The use of transgenic mice carrying human immunoglobulin (Ig) loci in their germline configuration provide for the isolation of high affinity fully human monoclonal antibodies directed against a variety of targets including human self antigens for which the normal human immune system is tolerant (Lonberg, N. et al., 1994, Nature 368:856–9; Green, L. et al., 1994, Nature Genet. 7:13–21; Green, L. & Jakobovits, 1998, Exp. Med. 188:483–95; Lonberg, N and Huszar, D., 1995, Int. Rev. Immunol. 13:65–93; Bruggemann, M. et al., 1991, Eur. J. Immunol. 21:1323–1326; Fishwild, D. et al., 1996, Nat. Biotechnol. 14:845–851; Mendez, M. et al., 1997, Nat. Genet. 15:146–156; Green, L., 1999, J. Immunol. Methods 231:11–23; Yang, X. et al., 1999, Cancer Res. 59:1236–1243; Brüggemann, M. and Taussig, M J., Curr. Opin. Biotechnol. 8:455–458, 1997). Human antibodies fall into a variety of different classes based on light chain (kappa and Lambda) and heavy chain (IgA1, IgA2, IgD, IgE, IgG1, IgG2, IgG3, IgG4, and IgM). These different classes potentially provide for different therapeutic uses. For example, the different heavy chain isotypes have different interactions with complement and with cell based Fc receptors. Some of the heavy chain classes (IgM and IgA) can also form multimers, thus increasing the valency of Fc and V region interactions. It is therefore desirable to have a platform for generating human monoclonal antibodies of all isotypes. However, the large size of human Ig loci (1–2 Mb) had been a major obstacle for the introduction of entire loci into transgenic mice to reconstitute full diverse human antibody repertoires because the cloning of over megabase-sized DNA fragments encompassing whole human Ig loci was difficult even with the use of yeast artificial chromosomes. Recently, a novel procedure using a human chromosome itself as a vector for transgenesis facilitated the transfer of the complete IgH and IgK loci into transgenic mice without the need for cloning DNA fragments into artificial DNA vectors (Tomizuka, K. et al., 1997, Nature Genet. 16:133–143; Tomizuka, K. et al., 2000, Proc. Natl. Acad. Sci. 97:722–727). Tomizuka et al. (Tomizuka, K. et al., 2000, Proc. Natl. Acad. Sci. U.S.A. 97:722–727) demonstrated the introduction of two transmittable human chromosome fragments (hCFs), one containing the immunoglobulin (Ig) heavy chain locus (IgH, ˜1.5 Mb) and the other the K light chain locus (IgH, ˜2 Mb), into a transgenic mouse strain whose endogenous IgH and IgK loci were inactivated. In the resultant double-transchromosomic (Tc)/double-knockout (KO) mice, a substantial proportion of the somatic cells retained both hCFs, and the rescue in the defect of Ig production was showed by high level expression of human Ig heavy and kappa light chains in the absence of mouse heavy and kappa light chains. In addition, serum expression profiles of four human Ig γ subclasses resembled those seen in humans. The transgenic mice developed an antigen-specific human antibody response upon immunization with human serum albumin (HSA), and HSA-specific human monoclonal antibodies with various isotypes were obtained from them. The study of Tomizuka et al. (ibid.) also demonstrated the instability of hChr.2-derived hCF containing the Igk locus (hCF(2-W23)) in mice. The observed instability of the κ transchromosome could be a impediment to optimal human kappa light chain expression and production of human kappa-positive hybridomas. Indeed, two-thirds of anti-HSA hybridomas obtained from a double-Tc/KO mouse were mouse lambda-positive (mλ+) and a majority (83%) of IgG/mX hybridomas was found to have lost the hCF(2-W23). Therefore, there is a need for transgenic animals that retain characteristics conferred by the transchromosomes described by Tomizuka et al. (ibid.), particularly animals that express substantially the full repertoire of human heavy chain isotypes, and also exhibit improved stability of introduced human sequences, allowing for increased efficiency of obtaining fully human antibodies.